Dantrolene sodium reverses the increase in cAMP response element and TPA responsive element DNA-binding activity in the rabbit brain following haloperidol administration and heat stress.
Using electrophoretic mobility-shift assay (EMSA), we examined DNA-binding activity of cAMP response element (CRE), onto its responsive element CRE, as well as TPA responsive element (TRE) in the medial hypothalamus and striatum of the experimental rabbits administered with haloperidol under heat stress exposure and studied the effects of dantrolene sodium to the transcriptional factor. In EMSA with nuclear extracts from the rabbit brain, the DNA-binding activities of CRE and TRE in medial hypothalamus and striatum increased following haloperidol and heat stress. These increases were maintained by coadministration with atropine. The treatment with dantrolene sodium markedly reversed such increases. The alterations of activities of these transcriptional factors may reflect the therapeutic effect of dantrolene sodium.
Tanii
H
H
Department of Neuropsychiatry, Osaka University Medical School, Japan.
Taniguchi
N
N
Tsujio
I
I
Asanuma
M
M
Iwata
E
E
Kudo
T
T
Ogawa
N
N
Takeda
M
M
D000818:Animals; D014150:Antipsychotic Agents / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D001923:Brain Chemistry / Q000187:drug effects*; D017362:Cyclic AMP Response Element-Binding Protein / Q000096:biosynthesis*; D004247:DNA / Q000096:biosynthesis*; D003620:Dantrolene / Q000627:therapeutic use*; D006220:Haloperidol / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D018882:Heat Stress Disorders / Q000378:metabolism*; D007031:Hypothalamus / Q000187:drug effects / Q000378:metabolism; D008297:Male; D009125:Muscle Relaxants, Central / Q000627:therapeutic use*; D017072:Neostriatum / Q000187:drug effects / Q000378:metabolism; D011817:Rabbits
D014150:Antipsychotic Agents; D017362:Cyclic AMP Response Element-Binding Protein; D009125:Muscle Relaxants, Central; D004247:DNA; D003620:Dantrolene; D006220:Haloperidol